PROJECT SUMMARY/ABSTRACT - Transgenic Mouse, ICSI and IVF Core The Transgenic Mouse Core was established during Phase I of the IBR COBRE based on novel transposase-mediated gene delivery and targeting technology developed at our institute by one of our COBRE investigators. During the first four years, the Core made significant progress towards the goal of becoming independently supported within fifteen years. We have accumulated a large array of equipment for micromanipulation of mouse gametes and embryo culture, and have recruited an experienced manager to head the Core laboratory. Before establishing the Core, we consulted with two established transgenic cores, one of which was COBRE supported at the University of Nevada. The IBR Core has made excellent progress, having produced 36 transgenic mouse lines, and developed new services that the COBRE investigators required that the Core was well suited to provide. The Core continued the development of novel gene delivery technology, including making significant progress on targeted gene insertion. Thus, the Core has contributed to the enhancement of the institution's research infrastructure by providing the COBRE investigators with transgenic mice and other services, research development, and training the next generation of scientists. In this Phase II application, we propose to enhance and transform the Core by expanding the services it provides through: (1) continued research and development to increase the efficiency of transgenic mouse production, and (2) a major renovation of animal and laboratory space that is being funded by the university as institutional support of the IBR COBRE. The Core will directly support four new COBRE Project Leaders. Because of this expansion, we have more accurately named it: the Transgenic Mouse, ICSI and IVF (TMII) Core. Dr. Stefan Moisyadi, the leader of the group that developed the new technology for gene insertion, and who was a Phase I junior investigator that graduated to independence, will become the TMII Core Director. These goals will be achieved through the following Specific Aims: Specific Aim 1. Improve the TMII Core through expansion of services, infrastructure development and renovation of the core laboratories. The Core will continue to provide transgenic mice using conventional technologies while incorporating rapidly emerging new technologies in the field, both from our own group and from others. We will also add new services such as ICSI and IVF to Project Leaders in Phase II. A $4 million renovation to the UH Manoa vivarium will allow transgenic mice to be produced much more efficiently. This will be an important step towards the development of our independence in Phase II. Specific Aim 2. Enhance and transform the IBR TMII Core through novel technology developed in Phase I of the IBR COBRE and the continued development of gene delivery systems. The TMII Core will continue to develop gene insertion technology during Phase II under the direction of Dr. Moisyadi.